When in 1551 the mismanagement of Sir William Dansell, King's Merchant to the Low Countries, had caused the English Government much financial embarrassment, the authorities called Gresham for advice, thereafter following his proposals. Gresham advocated the adoption of various methods – highly ingenious, but quite arbitrary and unfair — for raising the value of the pound sterling on the bourse of Antwerp which proved so successful that in just a few years King Edward VI had discharged almost all of his debts. The Government sought Gresham's advice in all their money difficulties, and also frequently employed him in various diplomatic missions. He had no stated salary, but in reward of his services received from King Edward various grants of lands, the annual value of which at that time amounted ultimately to about 400 pounds a year.

On the accession of Queen Mary in 1553 Gresham fell out of favour at Court for a short time with AldermanWilliam Dauntsey displacing him. But Dauntsey's financial operations proved unsuccessful and Gresham was soon re-instated; and as he professed his zealous desire to serve the Queen, and manifested great adroitness both in negotiating loans and in smuggling money, arms and foreign goods, not only were his services retained throughout her reign (1553–1558), but besides his salary of twenty shillings per diem he received grants of church lands to the yearly value of 200 pounds. Under Queen Elizabeth's reign (1558–1603), besides continuing in his post as financial agent of the Crown, Gresham acted as Ambassador Plenipotentiary to the Court of Duchess Margaret of Parma, Governor of the Netherlands, and was appointed a Knight Bachelor in 1559 prior to his departure. The unsettled times preceding the Dutch revolt compelled him to leave Antwerp on 10 March 1567; but, though he spent the remainder of his life in London, he continued his business as merchant and government financial agent in much the same way as he had always done. His enterprises made him one of the richest men of his generation in England.

Queen Elizabeth also found Gresham's abilities useful in a variety of other ways, including acting as gaoler to Lady Mary Grey (sister of Lady Jane Grey), who, as a punishment for marrying Thomas Keyes the sergeant-porter, was imprisoned in his house from June 1569 to the end of 1572.

In 1565 Gresham made a proposal to the City's Court of Aldermen to build, at his own expense, a bourse or exchange – what became the Royal Exchange, modelled on the Antwerpbourse – on condition that the Corporation provided for this purpose a suitable location. In this proposal he seems to have had a good eye for his self-interest as well as for the general good of the City's merchants, for by a yearly rental of £700 obtained for the shops in the upper part of the building he received more than sufficient return for his trouble and expense.

"Not in my life; yet I have been in Venice... In the Rialto there, called Saint Mark's; 'tis but a bauble, if compared to this. The nearest, that which most resembles this, is the great Burse in Antwerp, yet no comparable either in height or wideness, the fair cellarage, or goodly shops above. Oh my Lord Mayor, this Gresham hath much graced your City of London; his fame will long outlive him."[2]

In 1544 he married Anne Ferneley, widow of Sir William Read, a London merchant. By his wife he had an only son who predeceased him. He also had an illegitimate daughter who married Sir Nathaniel Bacon (c. 1546–1622), half-brother of Francis Bacon, 1st Viscount St Albans, becoming Anne, Lady Bacon.

Apart from some small sums to various charities, Gresham bequeathed the bulk of his property (consisting of estates in London and around England giving an income of more than 2,300 pounds a year) to his widow and her heirs, with the stipulation that after her death his own house in Bishopsgate Street and the rents from the Royal Exchange should be vested in the Corporation of London and the Mercers Company, for the purpose of instituting a college in which seven professors should read lectures, one each day of the week, in astronomy, geometry, physic, law, divinity, rhetoric and music. Thus, Gresham College, the first institution of higher learning in London, came to be established in 1597.

Gresham's Law (stated simply as: "Bad money drives out good") takes its name from him (although others, including the astronomer Nicolaus Copernicus, had recognised the concept for years) because he urged Queen Elizabeth to restore the debased currency of England. However, Sir Thomas never formulated anything like Gresham's Law, which was the 1857 conception of Henry Dunning Macleod, an economist with a knack for reading into a text that which was not written.[4]

According to ancient legend, the founder of the family, Roger de Gresham, was a foundling abandoned as a new-born baby among long grass in Norfolk during the 13th century and found there by a woman whose attention was drawn to the child by a grasshopper. Although a beautiful story, it is more likely that the grasshopper is simply a cantingheraldiccrest playing on the sound "grassh-" and "Gresh-". The Gresham family uses as its mottoFiat Voluntas Tua ('Thy will be done').[7]

The Gresham Hotel, Dublin is indirectly named after Gresham. It was established in 1817 by another Thomas Gresham, who was given that name as he was a foundling abandoned on the steps of the Royal Exchange;

Gresham appears as a background figure in a series of fictional mystery novels by the British author Valerie Anand writing under the pen-name of Fiona Buckley. The fictional heroine of the stories, Ursula Blanchard, lived in Antwerp with her first husband while he worked as one of Gresham's agents.

Gresham arms:Argent a Chevron Erminés between three Mullets pierced Sable

Sir Thomas Gresham's merchant's mark as depicted in the 1544 portrait of him owned by the Mercers' Company. Also as illustrated in Elmhirst, 1959,[9] with more pronounced "heart shape", used by other marks of this type, eg. the later HEICS mark